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Titolo:
A CYCLIC GMP-DEPENDENT AND G-KINASE-DEPENDENT EFFECT OF AZATHIOPRINE ON MIGRATION BY HUMAN NEUTROPHILS
Autore:
ELFERINK JGR; DAHA MR; DEKOSTER BM;
Indirizzi:
LEIDEN UNIV,DEPT MED BIOCHEM,POB 9503 NL-2300 RA LEIDEN NETHERLANDS LEIDEN UNIV,DEPT NEPHROL NL-2300 RA LEIDEN NETHERLANDS
Titolo Testata:
Cellular and molecular life sciences
fascicolo: 7, volume: 53, anno: 1997,
pagine: 593 - 599
SICI:
1420-682X(1997)53:7<593:ACGAGE>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE; RHEUMATOID-ARTHRITIS; LEUKOCYTE LOCOMOTION; CHEMOTACTIC FACTORS; INHIBITION; INVITRO; PENICILLAMINE; METHOTREXATE; ENHANCEMENT; STIMULATION;
Keywords:
NEUTROPHIL; AZATHIOPRINE; MERCAPTOPURINE; MIGRATION; CHEMOTAXIS; CGMP; G-KINASE; CD11B;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
J.G.R. Elferink et al., "A CYCLIC GMP-DEPENDENT AND G-KINASE-DEPENDENT EFFECT OF AZATHIOPRINE ON MIGRATION BY HUMAN NEUTROPHILS", Cellular and molecular life sciences, 53(7), 1997, pp. 593-599

Abstract

Relatively high concentrations of azathioprine had an inhibitory effect on interleukin 8 (IL-8)- or formyl-methionyl-leucyl-phenylalanine-activated (fMLP)-chemotaxis by human neutrophils. However, application of low concentrations of azathioprine in a concentration gradient gavea chemotactic stimulation to random migration. Stimulation of migration was maximal at a concentration of 5 mu M azathioprine; at higher concentrations stimulation decreased again. The activating effect of azathioprine is located in the mercaptopurine moiety of the molecule, since mercaptopurine also stimulated neutrophil migration. In contrast tosome other chemotactic agents such as fMLP and IL-8, an activating concentration (5 mu M) of azathioprine did not cause an upregulation of CD11b expression on neutrophils in suspension. High concentrations of azathioprine (1 mM) inhibited CD11b expression of fMLP- or IL-8- activated neutrophils; the latter could explain the inhibitory effect of azathioprine. Azathioprine caused a transient stimulation of cGMP level;inhibitors of guanylate cyclase inhibited azathioprine-stimulated migration, suggesting that cGMP was associated with the stimulating effect of azathioprine on migration. Antagonists of cGMP-dependent protein kinase (G-kinase) strongly inhibited azathioprine-activated migration,indicating that the effect of azathioprine proceeds via G-kinase. Theantagonists had only a marginal effect on inhibition of IL-8-activated chemotaxis by high concentrations of azathioprine, thus the G-kinaseseems not to be of great importance on the inhibitory effect of azathioprine.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/21 alle ore 03:43:35